In the Urologic Oncology Section of the Surgery Branch the effect of estrogen, LHRH and 5 alpha reductase inhibitors on prostate carcinoma are being evaluated. We also have described and characterized a model for humoral hypercalcemia in nude mice bearing a prostate carcinoma. This is the first description of a model for humoral hypercalcemia for prostate carcinoma. We have also found the hypercalcemic effect to be present in a number of other human prostate carcinomas in nude mice and nude rats. This indicates that the humoral hypercalcemia may be a more generalized effect of the tumor and not localized to the initial cell line in which the effect was observed. We have identified a parathyroid hormone-like factor which is produced by these prostate carcinoma cell lines and we are in the process of characterizing this factor. We have established the presence of bone resorptive activity in prostate carcinoma of tumor extracts and also in the conditioned media from prostate carcinoma cell lines. We are comparing this activity with that found in the hypercalcemia of malignancy seen with hypernephroma tumors. We have also identified as osteoblastic factor which is produced by the prostate carcinoma in tissue culture, i.e. the fact that the tumor-conditioned media stimulates thymidine and proline incorporation by the osteoblastic cell lines. We are in the process of further characterization of the substance, its effect on both osteosarcoma cell lines and human osteoblasts as well as its specificity for human bones and osteoblast precursors.